Squamous cell carcinoma of the penis is an uncommon but potentially fatal malignancy, especially in the presence of inguinal lymph node metastases. The morbidity of inguinal lymphadenectomy precludes its use as a staging procedure on all patients, and the inability to predict which patients will progress to nodal disease remains a difficult problem. This article describes our use of deoxyribonucleic acid flow cytometry on paraffin-embedded specimens of 17 consecutive patients with histologically-diagnosed squamous cell carcinoma of the penis. Our results suggest that patients with squamous cell carcinoma of the penis and a high DNA index may be at an increased risk of disease progression and therefore may be candidates for aggressive surgical management, and also suggest that DNA flow cytometry may be a reliable prognostic indicator for selecting which patients would benefit most from inguinal lymphadenectomy.